The glutamatergic system plays a role in certain common behavioral manifestations of posttraumatic stress disorder (PTSD), e.g. mechanisms of fear learning and anxious arousal. We propose to evaluate the efficacy of the mGlu2/3 receptor agonist pomaglumetad methionil in treating PTSD in a randomized, double-blind, placebo-controlled, phase II clinical trial. Key endpoints of this trial include structured diagnostic and self- report measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression. Evaluation of the differential efficacy of the mGlu2/3 agonist pomaglumetad methionil on symptom clusters that comprise the theory-driven and empirically-supported five-factor phenotypic model of PTSD symptoms will provide greater specificity regarding how this drug differentially modulates unique dimensions of the PTSD phenotype. Given the inhibitory effects of mGlu2/3 receptor agonists on stress-induced NE secretion, we predict that pomaglumetad methionil will have the most pronounced effect in mitigating anxious arousal symptoms.!
This application aims to determine the role of the mGlu2/3 agonist pomaglumetad methionil in the treatment of posttraumatic stress disorder (PTSD). We propose to recruit patients with PTSD, and will conduct a placebo- controlled, double-blind, randomized clinical trial. Key endpoints of this trial include structured diagnostic and self-repor measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression.
|Neumeister, Alexander; Seidel, Jordan; Ragen, Benjamin J et al. (2015) Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder. Psychoneuroendocrinology 51:577-84|
|Ragen, Benjamin J; Seidel, Jordan; Chollak, Christine et al. (2015) Investigational drugs under development for the treatment of PTSD. Expert Opin Investig Drugs 24:659-72|
|Pietrzak, Robert H; Huang, Yiyun; Corsi-Travali, Stefani et al. (2014) Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors. Neuropsychopharmacology 39:2519-28|